Human microRNA sequencing and cytomegalovirus infection risk after kidney transplantation
Copyright © 2024 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved..
Cytomegalovirus (CMV)-seropositive kidney transplant recipients (KTRs) with detectable CMV-specific cell-mediated immunity according to the QuantiFERON-CMV assay (QTF-CMV) are expected to have adequate immune protection. Nevertheless, a proportion of patients still develop CMV infection. Human microRNAs (hsa-miRNAs) are promising biomarkers owing to their high stability and easy detection. We performed whole blood miRNA sequencing in samples coincident with the first reactive QTF-CMV after transplantation or cessation of antiviral prophylaxis to investigate hsa-miRNAs differentially expressed according to the occurrence of CMV infection. One-year incidence of CMV viremia was 55.0% (median interval from miRNA sequencing sampling of 29 days). After qPCR validation, we found that hsa-miR-125a-5p was downregulated in KTRs developing CMV viremia within the next 90 days (ΔCt: 7.9 ± 0.9 versus 7.3 ± 1.0; P = .011). This difference was more evident among KTRs preemptively managed (8.2 ± 0.9 versus 6.9 ± 0.8; P < .001), with an area under the receiver operating characteristic curve of 0.865. Functional enrichment analysis identified hsa-miR-125a-5p targets involved in cell cycle regulation and apoptosis, including the BAK1 gene, which was significantly downregulated in KTRs developing CMV viremia. In conclusion, hsa-miR-125a-5p may serve as biomarker to identify CMV-seropositive KTRs at risk of CMV reactivation despite detectable CMV-CMI.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons - (2024) vom: 02. Feb. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Fernández-Ruiz, Mario [VerfasserIn] |
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| Links: |
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| Themen: |
Biomarkers |
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| Anmerkungen: |
Date Revised 18.02.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1016/j.ajt.2024.01.028 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM368192032 |
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| 520 | |a Cytomegalovirus (CMV)-seropositive kidney transplant recipients (KTRs) with detectable CMV-specific cell-mediated immunity according to the QuantiFERON-CMV assay (QTF-CMV) are expected to have adequate immune protection. Nevertheless, a proportion of patients still develop CMV infection. Human microRNAs (hsa-miRNAs) are promising biomarkers owing to their high stability and easy detection. We performed whole blood miRNA sequencing in samples coincident with the first reactive QTF-CMV after transplantation or cessation of antiviral prophylaxis to investigate hsa-miRNAs differentially expressed according to the occurrence of CMV infection. One-year incidence of CMV viremia was 55.0% (median interval from miRNA sequencing sampling of 29 days). After qPCR validation, we found that hsa-miR-125a-5p was downregulated in KTRs developing CMV viremia within the next 90 days (ΔCt: 7.9 ± 0.9 versus 7.3 ± 1.0; P = .011). This difference was more evident among KTRs preemptively managed (8.2 ± 0.9 versus 6.9 ± 0.8; P < .001), with an area under the receiver operating characteristic curve of 0.865. Functional enrichment analysis identified hsa-miR-125a-5p targets involved in cell cycle regulation and apoptosis, including the BAK1 gene, which was significantly downregulated in KTRs developing CMV viremia. In conclusion, hsa-miR-125a-5p may serve as biomarker to identify CMV-seropositive KTRs at risk of CMV reactivation despite detectable CMV-CMI | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a RNA-sequencing | |
| 650 | 4 | |a biomarkers | |
| 650 | 4 | |a cytomegalovirus | |
| 650 | 4 | |a kidney transplantation | |
| 650 | 4 | |a miR-125a-5p | |
| 650 | 4 | |a microRNAs | |
| 700 | 1 | |a López-García, Ángela |e verfasserin |4 aut | |
| 700 | 1 | |a Valverde-Manso, Andrea |e verfasserin |4 aut | |
| 700 | 1 | |a Parra, Patricia |e verfasserin |4 aut | |
| 700 | 1 | |a Rodríguez-Goncer, Isabel |e verfasserin |4 aut | |
| 700 | 1 | |a Ruiz-Merlo, Tamara |e verfasserin |4 aut | |
| 700 | 1 | |a López-Medrano, Francisco |e verfasserin |4 aut | |
| 700 | 1 | |a González, Esther |e verfasserin |4 aut | |
| 700 | 1 | |a Polanco, Natalia |e verfasserin |4 aut | |
| 700 | 1 | |a San Juan, Rafael |e verfasserin |4 aut | |
| 700 | 1 | |a Andrés, Amado |e verfasserin |4 aut | |
| 700 | 1 | |a Aguado, José María |e verfasserin |4 aut | |
| 700 | 1 | |a Redondo, Natalia |e verfasserin |4 aut | |
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